DESCRIPTION (Investigator's abstract): This application is for competitive renewal of an NIMH Research Scientist Development Award. The University of California, Los Angeles (UCLA) is the nominating institution and the site of most of the planned research and career development activities. The chief objective of the proposal is to foster the continued development of the P1 as an investigator working at the boundary between molecular human genetics and psychiatry. The P1's laboratory is mainly focused on the use of molecular and population genetics approaches to identify the chromosomal location of genes responsible for bipolar disorder (BP), to clone these genes and then to characterize their function. The proposal outlines these objectives and the plans for achieving them. The new goals represent a natural extension of those enunciated in the current award, and are based on developments in human genetics and genomics, as a whole, but particularly on work accomplished in the PI's laboratory during the past four years. Identifying genes responsible for BP will lead to re-evaluation of the diagnostic categories that are currently in place for mood disorders. Mapping and cloning BP genes will be of great scientific significance and will likely also have important implications for clinical practice. The proposed population genetics studies aimed mainly at understanding factors governing the detection of linkage disequilibrium (LD) in the genome and on improving the methods available for LD analysis, will yield information that may be valuable in mapping loci for BP as well as other psychiatric disorders. Additionally, the P1's laboratory has developed a new project focused on pharmacogenetic studies of neurotransmitter transporter genes. The goal of these studies is to systematically identify sequence variants in these genes and then to determine if such variants are associated with treatment response to or side effects from psychopharmacologic agents, in particular antidepressant drugs. These studies may lead to more focused used of such agents in clinical practice. Some of the projects proposed in this application will be carried out in collaboration with investigators who have already contributed to the P1's development as a scientist, while other proposed projects will be carried out with new collaborators.